Increased BAX expression is associated with an increased risk of relapse in childhood acute lymphocytic leukemia

Studies in cell lines have indicated that expression of the BCL-2 family of proteins is an important determinant of chemotherapy-induced apoptosis; ho wever, the level of expression of these proteins in childhood acute lymphob lastic leukemia (ALL) has not been extensively reported. Using quantitative Western blotting we have determined the level of expression of BCL-9, BAX, MCL-1, and BCL-X in lymphoblasts from 47 children with ALL (33 at presenta tion only, 4 at relapse only, and 10 at both presentation and on relapse). Results were determined as a ratio to actin as an internal control. BCL-2. BAX, and MCL-1 were detected in all samples. BCL-X-L was only detected in 6 cases (4 at presentation and 2 at relapse) and BCL-X-S in none. No correla tion was found between expression and white blood cell count, age at diagno sis, gender, or blast karyotype. BCL-2 levels and the BCL/BAX and MCL-1/BAX ratios were found to be significantly higher in B-lineage as compared with T-lineage disease (P < .003, .02, and .02, respectively). No consistent pa ttern of change in expression was noted in the 10 cases studied at both pre sentation and relapse. Kaplan-Meier analysis showed a significant correlati on between high BAX expression and an increased probability of relapse (P < .05 by the log rank test), suggesting that chemosensitivity in leukemic bl asts may be regulated by factors that override the BCL-2 pathway. (C) 1999 by The American Society of Hematology.